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2007 Grant - Bloom

Signaling From Beta-Amyloid Through Tau in Alzheimer's Disease

George S. Bloom, Ph.D.
University of Virginia
Charlottesville, Virginia

2007 Investigator-Initiated Research Grant

Amyloid plaques and neurofibrillary tangles are two of the primary pathologic features of Alzheimer's disease. Amyloid plaques occur outside of nerve cells in the brain and are partly made of beta-amyloid, a protein fragment. Neurofibrillary tangles occur inside nerve cells and are made of an altered protein called tau. Researchers have long suspected that amyloid plaques and neurofribrillary tangles are related mechanistically, such that the occurrence of one leads to the other. But the nature of this relationship has not been discovered.

George Bloom, Ph.D., and colleagues have been studying the relationship between amyloid plaques and neurofibrillary tangles in cultured nerve cells. They found that a specific, early occurring version of beta-amyloid disrupts microtubules, tiny structures that serve as a support "scaffolding" inside cells. This disruptive effect occurs only in cells that contain tau (such as nerve cells). The researchers suspect, therefore, that some interaction between beta-amyloid and tau is involved in the nerve cell death that occurs after the cells are exposed to beta-amyloid.

Dr. Bloom and colleagues plan to continue their studies of how beta-amyloid and tau interact and how this interaction causes disruption of nerve cells and eventually cell death. They expect to uncover a complex series of biochemical steps involved in this process. Each step is a potential target for the development of drugs to block the toxicity of beta-amyloid, thereby slowing or halting the progression of Alzheimer's disease.